Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Interaction of the human T cell leukemia virus-I transactivator protein Tax with the host cell transcriptional machinery.
Diss Abstr Int [B]; 53(6):2692 1992. Unique Identifier : AIDSLINE ICDB/93690097 Matthews MH; Univ. of Colorado at Boulder
Abstract:
The Tax protein, encoded by human T cell leukemia virus-I (HTLV-I), is a potent transactivator of transcription. Because several of the genes transactivated by Tax are involved in regulation of cell growth, it is thought that transactivation may contribute to viral oncogenesis. Unlike a number of other viral oncogenes, the tax gene has no obvious sequence similarity to cellular genes, and the mechanism by which the Tax protein interacts with the host cell transcriptional machinery is poorly understood. To begin to characterize the biochemical mechanism of Tax-mediated transactivation, I developed a Tax-responsive in vitro transcription system. Tax was purified from cells infected with a baculovirus expression vector. Addition of these Tax preparations to nuclear extracts from uninfected human T lymphocytes activated transcription of the HTLV-I promoter approx 10-fold. As expected, the effect of recombinant Tax was diminished in HTLV-I-infected T-lymphocyte extracts containing endogenous Tax. Transcriptional stimulatory activity copurified with the immunoreactive 40-kD Tax polypeptide on gel filtration chromatography. Only monomeric Tax was active, and it was necessary to remove aggregated Tax from preparations to obtain transcriptional stimulation. Tax-mediated transactivation in vivo has been previously shown to require 21-bp repeat-Tax responsive elements (TxREs) in the promoter DNA. Stimulation of transcription in vitro was also strongly dependent on these sequences. Since Tax does not bind directly to the TxRE, it likely acts through host cell factors. To further investigate the mechanism of Tax transactivation, I purified cellular proteins that bind the 21-bp repeat TxRE using DNA affinity chromatography. Recombinant Tax markedly increased the formation of a specific host protein-DNA complex detected in an electrophoretic mobility shift assay. These data suggest that Tax activates transcription through a direct interaction with cellular proteins that bind to the 21-bp repeat TxRE. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD92-32710.)
Keywords: Cell Transformation, Viral Gene Products, tax/*METABOLISM Human HIV Long Terminal Repeat/GENETICS HTLV-I/*GENETICS/METABOLISM HTLV-I Infections/GENETICS/METABOLISM Promoter Regions (Genetics) T-Lymphocytes/METABOLISM *Transcription, Genetic THESIS 930630
M9361084
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
